This invention relates generally to nanoscale devices, and more particularly relates to nanoscale devices for detecting and analyzing species such as molecules components of molecules.
The detection, analysis, and quantification of biological and chemical species, such as DNA, has become the central focus of a wide range of applications for areas of healthcare and the life sciences, ranging from diagnosis of disease to discovery and screening of new drug molecules. Of particular interest is an ability to carry out single molecule sensing. The ability to study a biological system one molecule at a time enables observation of, e.g., time trajectories and characterization of biological pathways, offering fundamental insight into biophysical problems.
There have been proposed a wide range of nanopore-based structures for molecular sensing. Nanopores are generally considered to be apertures having a diameter on the nanoscale. It has been suggested to translocate a strand of DNA through a solid-state nanometer-diameter pore provided in an ionic solution to measure the blockage of ionic current through the nanopore during the DNA translocation. But the small ionic current differences resulting from the translocation of different DNA bases are generally beyond the resolution limit of conventional current amplifiers because the intrinsic noise due to the charged DNA bases is so large, and it is therefore not possible to discriminate between specific bases. To overcome this low signal-to-noise ratio, it has been proposed to alternatively employ an electronic sensing arrangement, or electronic sensor, such as a tunneling junction, at the site of a nanopore, for sensing molecules translocating through the nanopore. While such configurations are expected to provide an improved signal-to-noise ratio, they cannot, in general, achieve single nucleotide sensitivity.